1. Field of the Invention
The present invention relates to a novel process for preparing .beta.-lactam derivatives, which are useful antibiotics, having the formula (I): ##STR3## wherein R.sup.1 represents hydrogen or a metal salt; and R.sup.2 represents hydrogen, acetoxy methyl, (2,5-dihydro-2-methyl-6-hydroxy-5-oxo-as-triazin-3-yl)thiomethyl or (1-methyl-1H-tetrazol-5-yl)thiomethyl.
2. Description of the Prior Art
Hitherto, a number of processes for the preparation of semi-synthesized .beta.-lactam antibiotic materials have been proposed.
For instance, it is well known that an acylated compound of the formula (I) above can be prepared by converting an amino-protected organic acid of the formula (II): ##STR4##
wherein R.sup.3 is an amino-protecting group, into its activated derivatives, and then by acylating 7-ADCA (7-aminodesacetoxycephalosporanic acid), 7-ACA (7-aminocephalosporanic acid) or its derivatives with the activated derivatives.
The activated derivatives of the compound of the formula (II) may include an acid chloride, an acid anhydride, an activated ester, an activated amide, an activated amide solvate, and so forth.
In order to use an acid chloride as the activated derivative, the organic acid (II) is reacted with thionyl chloride (SOCl.sub.2), phosphorous trichloride (PCl.sub.3), phosphorous pentachloride (PCl.sub.5), or phosphorous oxychloride (POCl .sub.3). The resulting acid chloride is acylated with 7-ADCA, 7-ACA or its derivatives followed by removing the protecting R.sup.3 group to give a compound of the formula (I): see Japanese Laid-Open (Kokai) Patent Publication Nos. 52-102,096; 53-34,795; 53-68,796; 54-52,096; and 54-157,596; as well as U.K. Patent No. 2,025,933.
However, the process mentioned above must be carried out under severe and complicated reaction conditions, because the process is subject to protection and deprotection of the amino group in the organic acid. This process further suffers from the defect that the acid chloride is unstable.
In another method, 2-pyridinethioester, 2-benzothiazole ester, or 1-hydroxy benzotriazole ester is synthesized from an organic acid of the formula (III): ##STR5## and then the resulting ester is acylated with 7-ADCA, 7-ACA or its derivatives to give a compound of the formula (I): see Japanese Laid-Open (Kokai) Patent Publication No. 52-102,293; 54-95,593; and 56-152,488.
However, this process shows relatively low yields due to a side reaction accompanied when preparing the activated esters. Furthermore the process must be carried out at a high reaction temperature for a long period of reaction time during the acylation step, and requires a step of removing the by-products resulted from the process.
It has also been reported that in order to resolve the problems encountered in utilizing the activated esters, an activated amide solvate of a compound of the formula (III) is isolated from an organic solvent, and then is acylated with 7-ACA or its derivatives to give a compound of the formula (I): see European Patent No. 175,814. However, this process has the disadvantages that it is difficult to isolate the activated amide solvate from the organic solvent used, and that it must be carried out under the substantially similar reaction conditions to those in the cases involving an activated ester or an activated amide, requiring a high reaction temperature and a long period of reaction time.
Meanwhile, T. Fujisawa et al. have reported in Chem. Letters, 1267 (1983) that a lithium carboxylate derivative is reacted with dichlorophosphoran to give a corresponding acyloxyphosphonium salt derivative, and then the resulting acyloxyphosphonium salt is reacted with a Grignard reagent to give a corresponding diketone.